We continue to investigate reasons for the disparate response to therapy of tumors in our model. Comparison was made of the cytotoxicity of SpC and RLNCs from animals demonstrating a good response to chemo-immunotherapy with those exhibiting a poor response. An evaluation was made of the capability of those cells to transfer cytotoxicity to normal recipients. SpC or LNC cytotoxicity after transfer was similar whether mice were recipients of cells from responders, nonresponders or untreated animals. Transfer of normal but not tumor sensitized SpC to a tumor bearer results in increased cytotoxicity of that animal. We hypothesized that there may be a shortage of uncommitted cells available for recruitment in the tumor bearer. Consequently, one group of tumor bearing mice received normal SpC in addition to CY and CP and another no cells with that treatment. The addition of SpC did not result in a more uniform therapeutic response. Increasing evidence indicates heterogeneity of cells comprising a tumor. Since the tumor employed in our model is a mammary carcinoma it is possible that response to therapy may be related to the estrogen receptor (ER) content of the tumor. Extensive effort has been devoted to the use of 17-FE ligand of Dandliker for the determination of ER. Prior to employing the method for ascertaining ER in responders and nonresponders to therapy it was necessary to determine the validity, specificity, reproducibility of the method and to optimize the technic. Studies during the eight months covered in this report have shown the C3H mammary tumor used in this laboratory contains approximately 30% fluorescent (ER plus) cells. Normal uterus and liver cells also contain ER. Fluorsecence in the tumor and uterus is located in the nucleus, nucleolus and/or cytoplasm. In the liver only cytoplasmic fluorescence occurs. Fluorescence can be blocked in vitro by tamoxifen or estradiol. Tumors containing 20-28% ER plus cells demonstrated 8-13 fmol ER/mg cytosol protein. During the coming year both ER and kinetics will be related to response to chemo-, immuno-, and anti-estrogen therapies.